The v-sis oncogene of simian sarcoma virus (SSV) encodes a protein which is closely related to the human PDGF-B or -2 chain. The c-sis/platelet-derived growth factor (PDGF)-B gene. The human homologue for v-sis. has been cloned and characterized. When this gene is expressed under the control of a retrovirus promoter and introduced in NIH 3T3 cells in culture, it confers the transformed phenotype to these cells. The PDGF-B chain transcript has been observed in a variety of human glioblastomas and fibrosarcomas. In contrast, this transcript is not detectable in normal glial cells or fibroblasts. All of these findings along with the immunological demonstration of the PDGF-B product expressed by such human tumor cells support a role of PDGF-B in tumorigenesis. We have investigated the regulation of expression of this growth factor in vivo and in vitro. Overexpression of PDGF-B in vivo leads to formation of fibrosarcomas in mice. Low levels of expression of this human growth factor in different tissues was also achieved by introducing the gene into the germline of transgenic mice.